The river is strongly associated with the Gambia, the smallest country in mainland Africa, which consists of little more than the downstream half of the river and its two banks.

From the Fouta Djallon, the river runs northwest into the Tambacounda Region of Senegal, where it flows through the Parc National du Niokolo Koba, then is joined by the Nieri Ko and Koulountou before entering the Gambia at Fatoto. At this point the river runs generally west, but in a meandering course with a number of oxbows, and about 100km from its mouth it gradually widens, to over 10km wide where it meets the sea.